System and method for the pretreatment of the endplates of an intervertebral disc

ABSTRACT

A method for the pre-treatment of an intervertebral disc prior to the introduction of a disc prosthesis or implant includes removing at least a portion of the nucleus pulposus of the intervertebral disc to expose at least a portion of the endplate of an adjacent vertebra to the disc. A fluent treatment material is then injected into the disc space to come into contact with the portion of the endplate. The fluent treatment material is operable to prepare the portion of the endplate to accommodate a disc prosthesis, implant or graft subsequently introduced into the disc space. Different fluent treatment materials are provided that depend upon the condition of the vertebral endplates.

REFERENCE TO RELATED APPLICATIONS

This application claims priority to provisional application Ser. No.60/336,002, entitled “Devices, Methods and Assemblies for IntervertebralDisc Repair and Regeneration”, and provisional application Ser. No.60/336,332, entitled “Pretreatment of Cartilaginous Endplates Prior toTreatment of the Intervertebral Disc with an Injectable Biomaterial”,both of which were filed on Nov. 1, 2001, and the disclosure of whichare both incorporated herein by reference.

BACKGROUND OF THE INVENTION

The present invention relates generally to the treatment of spinaldiseases and injuries, and more specifically to the restoration of thespinal disc following the treatment. The invention contemplates devicesand methods for restoring the normal intervertebral disc space heightand for facilitating the introduction of biomaterials for use in therepair and restoration of the intervertebral disc.

The intervertebral disc is divided into two distinct regions: thenucleus pulposus and the annulus fibrosus. The nucleus lies at thecenter of the disc and is surrounded and contained by the annulus. Theannulus contains collagen fibers that form concentric lamellae thatsurround the nucleus and insert into the endplates of the adjacentvertebral bodies to form a reinforced structure. Cartilaginous endplatesare located at the interface between the disc and the adjacent vertebralbodies.

The intervertebral disc is the largest avascular structure in the body.The cells of the disc receive nutrients and expel waste by diffusionthrough the adjacent vascularized endplates. The hygroscopic nature ofthe proteoglycan matrix secreted by cells of the nucleus operates togenerate high intra-nuclear pressure. As the water content in the discincreases, the intra-nuclear pressure increases and the nucleus swellsto increase the height of the disc. This swelling places the fibers ofthe annulus in tension. A normal disc has a height of about 10-15 mm.

There are many causes of disruption or degeneration of theintervertebral disc that can be generally categorized as mechanical,genetic and biochemical. Mechanical damage includes herniation in whicha portion of the nucleus pulposus projects through a fissure or tear inthe annulus fibrosus. Genetic and biochemical causes can result inchanges in the extracellular matrix pattern of the disc and a decreasein biosynthesis of extracellular matrix components by the cells of thedisc. Degeneration is a progressive process that usually begins with adecrease in the ability of the extracellular matrix in the centralnucleus pulposus to bind water due to reduced proteoglycan content. Witha loss of water content, the nucleus becomes desiccated resulting in adecrease in internal disc hydraulic pressure, and ultimately to a lossof disc height. This loss of disc height can cause the annulus to bucklewith non-tensile loading and the annular lamellae to delaminate,resulting in annular fissures. Herniation may then occur as ruptureleads to protrusion of the nucleus.

Proper disc height is necessary to ensure proper functionality of theintervertebral disc and spinal column. The disc serves severalfunctions, although its primary function is to facilitate mobility ofthe spine. In addition, the disc provides for load bearing, loadtransfer and shock absorption between vertebral levels. The weight ofthe person generates a compressive load on the discs, but this load isnot uniform during typical bending movements. During forward flexion,the posterior annular fibers are stretched while the anterior fibers arecompressed. In addition, a translocation of the nucleus occurs as thecenter of gravity of the nucleus shifts away from the center and towardsthe extended side.

Changes in disc height can have both local and global effects. On thelocal (or cellular, level) decreased disc height results in increasedpressure in the nucleus, which can lead to a decrease in cell matrixsynthesis and an increase in cell necrosis and apoptosis. In addition,increases in intra-discal pressure create an unfavorable environment forfluid transfer into the disc, which can cause a further decrease in discheight.

Decreased disc height also results in significant changes in the globalmechanical stability of the spine. With decreasing height of the disc,the facet joints bear increasing loads and may undergo hypertrophy anddegeneration, and may even act as a source of pain over time. Decreasedstiffness of the spinal column and increased range of motion resultingfrom loss of disc height can lead to further instability of the spine,as well as back pain. The outer annulus fibrosus is designed to providestability under tensile loading, and a well-hydrated nucleus maintainssufficient disc height to keep the annulus fibers properly tensioned.With decreases in disc height, the annular fibers are no longer able toprovide the same degree of stability, resulting in abnormal jointmotion. This excessive motion can manifest itself in abnormal muscle,ligament and tendon loading, which can ultimately be a source of backpain.

Radicular pain may result from a decrease in foraminal volume caused bydecreased disc height. Specifically, as disc height decreases, thevolume of the foraminal canal, through which the spinal nerve rootspass, decreases. This decrease may lead to spinal nerve impingement,with associated radiating pain and dysfunction

Finally, adjacent segment loading increases as the disc height decreasesat a given level. The discs that must bear additional loading are nowsusceptible to accelerated degeneration and compromise, which mayeventually propagate along the destabilized spinal column.

In spite of all of these detriments that accompany decreases in discheight, where the change in disc height is gradual many of the illeffects may be “tolerable” to the spine and may allow time for thespinal system to adapt to the gradual changes. However, the suddendecrease in disc volume caused by the surgical removal of the disc ordisc nucleus may heighten the local and global problems noted above.Many disc defects are treated through a surgical procedure, such as adiscectomy in which the nucleus pulposus material is removed. During atotal discectomy, a substantial amount (and usually all) of the volumeof the nucleus pulposus is removed and immediate loss of disc height andvolume can result. Even with a partial discectomy, loss of disc heightcan ensue. Discectomy alone is the most common spinal surgicaltreatment, frequently used to treat radicular pain resulting from nerveimpingement by disc bulge or disc fragments contacting the spinal neuralstructures.

In another common spinal procedure, the discectomy may be followed by animplant procedure in which a prosthesis is introduced into the cavityleft in the disc space when the nucleus material is removed. Thus far,the most prominent prosthesis is a mechanical device or a “cage” that issized to restore the proper disc height and is configured for fixationbetween adjacent vertebrae. These mechanical solutions take on a varietyof forms, including solid kidney-shaped implants, hollow blocks filledwith bone growth material, push-in implants and threaded cylindricalcages.

In more recent years, injectable biomaterials have been more widelyconsidered as an augment to a discectomy. As early as 1962, AlfNachemson suggested the injection of room temperature vulcanizingsilicone into a degenerated disc using an ordinary syringe. In 1974,Lemaire and others reported on the clinical experience of Schulman withan in situ polymerizable disc prosthesis. Since then, many injectablebiomaterials or scaffolds have been developed as a substitute for thedisc nucleus pulposus, such as hyaluronic acid, fibrin glue, alginate,elastin-like polypeptides, collagen type I gel and others. A number ofpatents have issued concerning various injectable biomaterialsincluding: cross-linkable silk elastin copolymer discussed in U.S. Pat.No. 6,423,333 (Stedronsky et al.); U.S. Pat. No. 6,380,154 (Capello etal.); U.S. Pat. No. 6,355,776 (Ferrari et al.); U.S. Pat. No. 6,258,872(Stedronsky et al.); U.S. Pat. No. 6,184,348 (Ferrari et al.); U.S. Pat.No. 6,140,072 (Ferrari et al.); U.S. Pat. No. 6,033,654 (Stedronsky etal.); U.S. Pat. No. 6,018,030 (Ferrari et al.); U.S. Pat. No. 6,015,474(Stedronsky); U.S. Pat. No. 5,830,713 (Ferrari et al.); U.S. Pat. No.5,817,303 (Stedronsky et al.); U.S. Pat. No. 5,808,012 (Donofrio etal.); U.S. Pat. No. 5,773,577 (Capello); U.S. Pat. No. 5,773,249(Capello et al.); U.S. Pat. No. 5,770,697 (Ferrari et al.); U.S. Pat.No. 5,760,004 (Stedronsky); U.S. Pat. No. 5,723,588 (Donofrio); U.S.Pat. No. 5,641,648 (Ferrari); and U.S. Pat. No. 5,235,041 (Capello etal.); protein hydrogel described in U.S. Pat. No. 5,318,524 (Morse etal.); U.S. Pat. No. 5,259,971 (Morse et al.): U.S. Pat. No. 5,219,328(Morse et al.); and U.S. Pat. No. 5,030,215; polyurethane-filledballoons discussed in 60/004,710 (Felt et al.); U.S. Pat. No. 6,306,177(Felt et al.); U.S. Pat. No. 6,248,131 (Felt et al.) and U.S. Pat. No.6,224,630 (Bao et al.); collagen-PEG set forth in U.S. Pat. No.6,428,978 (Olsen et al.); U.S. Pat. No. 6,413,742 (Olsen et al.); U.S.Pat. No. 6,323,278 (Rhee et al.); U.S. Pat. No. 6,312,725 (Wallace etal.); U.S. Pat. No. 6,277,394 (Sierra); U.S. Pat. No. 6,166,130 (Rhee etal.); U.S. Pat. No. 6,165,489 (Berg et al.); U.S. Pat. No. 6,123,687(Simonyi et al.); U.S. Pat. No. 6,111,165 (Berg); U.S. Pat. No.6,110,484 (Sierra); U.S. Pat. No. 6,096,309 (Prior et al.); U.S. Pat.No. 6,051,648 (Rhee et al.); U.S. Pat. No. 5,997,811 (Esposito et al.);U.S. Pat. No. 5,962,648 (Berg); U.S. Pat. No. 5,936,035 (Rhee et al.);and U.S. Pat. No. 5,874,500 (Rhee et al.); chitosan in U.S. Pat. No.6,344,488 to Chenite et al.; a variety of polymers discussed in U.S.Pat. No. 6,187,048 (Milner et al.; recombinant biomaterials in60/038,150 (Urry); U.S. Pat. No. 6,004,782 (Daniell et al.); U.S. Pat.No. 5,064,430 (Urry); U.S. Pat. No. 4,898,962 (Urry); U.S. Pat. No.4,870,055 (Urry); U.S. Pat. No. 4,783,523 (Urry et al.); U.S. Pat. No.4,783,523 (Urry et al.); U.S. Pat. No. 4,589,882 (Urry); U.S. Pat. No.4,500,700 (Urry); U.S. Pat. No. 4,474,851 (Urry); U.S. Pat. No.4,187,852 (Urry et al.); and U.S. Pat. No. 4,132,746 (Urry et al.); andannulus repair materials described in U.S. Pat. No. 6,428,576 toHaldimann.

These references disclose biomaterials or injectable scaffolds that haveone or more properties that are important to disc replacement, includingstrong mechanical strength, promotion of tissue formation,biodegradability, biocompatibility, sterilizability, minimal curing orsetting time, optimum curing temperature, and low viscosity for easyintroduction into the disc space. The scaffold must exhibit thenecessary mechanical properties as well as provide physical support. Itis also important that the scaffold be able to withstand the largenumber of loading cycles experienced by the spine. The biocompatibilityof the material is of utmost importance. Neither the initial materialnor any of its degradation products should elicit an unresolved immuneor toxicological response, demonstrate immunogenicity, or expresscytoxicity.

Generally, the above-mentioned biomaterials are injected as viscousfluids and then cured in situ. Curing methods include thermosensitivecross-linking, photopolymerization, or the addition of a solidifying orcross-linking agent. The setting time of the material is important—itshould be long enough to allow for accurate placement of the biomaterialduring the procedure yet should be short enough so as not to prolong thelength of the surgical procedure. If the material experiences atemperature change while hardening, the increase in temperature shouldbe small and the heat generated should not damage the surroundingtissue. The viscosity or fluidity of the material should balance theneed for the substance to remain at the site of its introduction intothe disc, with the ability of the surgeon to manipulate its placement,and with the need to assure complete filling of the intradiscal space orvoids.

Since the intervertebral disc is an avascular structure, it relies uponthe vascularized adjacent vertebral bodies to receive nutrients andexpel waste. This fluid flow occurs by diffusion through the vertebralendplates. Thus, as shown in FIG. 1, a spinal disc D is disposed betweenadjacent vertebrae V₁ and V₂. The disc includes the annulus fibrosus A,which surrounds and contains the nucleus pulposus N. The portion of theadjacent vertebrae in contact with the nucleus constitutes the endplatesE₁ and E₂.

As depicted in the figure, the bony vertebral bodies V₁ and V₂ arevascularized, as represented by the blood vessels B. The vertebralbodies are porous so fluid can pass to and from the vessels B. Inparticular, fluids traverse the semi-permeable cartilaginous endplatesE₁ and E₂ as represented by the arrows entering and leaving the nucleusN. Fluids entering the nucleus provide nutrients to the cells of thenucleus, while fluids expelled from the disc constitute cellularmetabolic waste products. The nutrients are required for cell metabolismand manufacture of extracellular matrix (e.g., collagen, proteoglycans,etc.) by the cells of the disc. This extracellular matrix provides thestructure needed to resist mechanical loads and maintain normalanatomical relationships between the adjacent vertebrae. The metabolicwaste products must be removed to prevent their accumulation within thedisc, which build-up can lead to conditions less favorable to cellproliferation or synthesis (e.g., altered pH). Water can also diffusethrough the endplates to maintain a proper intra-discal pressure, whichultimately results in an appropriate disc height.

Disc degeneration (discussed above) can result from decreases in cellnutrition and declining disc cell viability may occur through a varietyof mechanisms. One common mechanism involves decreased diffusion throughthe adjacent vertebral endplates E₁ and E₂. The endplates arecartilaginous and have a thickness ranging from 0.1 mm in the regionover the nucleus N to 1.6 mm at the region of the annulus fibrosus A.The endplates are also vascularized via arterioles and venousinvaginations. With many types of disc degeneration, the endplates canthicken or lose vascularization, becoming increasingly impermeable andsclerotic.

As the endplates become more impermeable, diffusion through theendplates decreases. This decreased diffusion can lead to decreasedtransfer of nutrients to the disc cells, lower pH, reduced oxygentension and increased cell apoptosis (programmed cell death) andnecrosis. Ultimately, the altered cellular viability leads to reducedmatrix synthesis by the cells of the disc. Cells under decreasednutritional influx and waste byproduct outflow are unable to synthesizethe matrix needed to maintain the specialized matrix of the nucleuspulposus and inner annulus fibrosus. This specialized matrix consists ofcollagen and proteoglycans capable of resisting the high compressiveforces exerted on the disc. The negatively charged branching structureson the large and small proteoglycans bind large amounts of water andprovide for the viscoelastic properties of the healthy disc. Withdecreases in proteoglycan content, the intervertebral disc becomesprogressively desiccated, which ultimately leads to the loss in discheight and increased instability discussed above.

Extracellular matrix forms both adjacent to the cells and distributedbetween the cells. The matrix distributed widely between the cellsprovides the overall structure needed by the nucleus pulposus to resistmechanical loading. The matrix formed adjacent to the cells (thepericellular matrix) is important in shielding the individual cells fromexcessive loading that could trigger gene expression changes (e.g.,decreased synthesis of mRNA for matrix proteins), and could ultimatelylead to cell apoptosis and necrosis. Decreased matrix synthesis in theface of poor nutrition and increased matrix breakdown by proteases,activated by the changing pH and oxygen tension, lead to progressivedegeneration of the disc and increased vulnerability to repetitivetrauma.

Frequently, and perhaps typically, disc degeneration and/or herniationis preceded by degeneration of the vertebral endplates. Treatment of thedisc degeneration can proceed as outlined above—i.e., a discectomyfollowed by the introduction of some form of scaffold into theintradiscal space. In some cases, the scaffold is a solid implant orspinal fusion that does not preserve any of the mechanical properties ofthe disc. In many spinal fusions, the endplate is reduced to “bleedingbone” by means of a rongeur or rasp to enhance the fixation of thefusion implant to the adjacent vertebrae. In other fusion procedures,portions of the adjacent vertebrae are removed to make room for thefusion implant. In these cases, viability of the endplates is relativelyunimportant.

However, where the scaffold is of the type described above that seeks torestore normal disc function (at least as much as possible), patency ofthe endplates is of critical concern. If the disc has sclerotic orthickened endplates, no restorative scaffold will work in its intendedway because no fluid diffusion is permitted. In other words, if thefoundation is deficient, the entire treatment of the disc will fallshort of its goal.

Placement of cells within a matrix (or migration of cells into a matrix)is destined to fail if these cells cannot receive adequate nutrients orcannot expel metabolic products. For tissue engineering of the disc tobe a viable reparative and regenerative strategy, the diseased endplatemust be addressed in addition to the diseased intervertebral disc.

SUMMARY OF THE INVENTION

The present invention contemplates a method and system for addressingthe diseased vertebral endplates in anticipation of treatment for adegenerative or diseased intervertebral disc. One step of the methodcalls for removing at least a portion of the nucleus pulposus of theintervertebral disc to expose at least a portion of the endplate of anadjacent vertebra to the disc. The method then includes the step ofinjecting a fluent treatment material into the disc space to come intocontact with the portion of the endplate. The fluent treatment materialis operable to prepare the portion of the endplate to accommodate a discprosthesis, implant or graft subsequently introduced into the discspace.

In one aspect of the invention, the fluent treatment material isretained within the disc space for an incubation period sufficient forsubstantially complete operation of the fluent treatment material on theportion of the endplate. The fluent material and any byproducts of itsoperation of the fluent treatment material on the portion of theendplate can be removed by lavage and flushing.

In some embodiments, the step of injecting a fluent treatment materialincludes simultaneously maintaining the vertebrae adjacent to the discin a distracted position. In specific embodiments, this step includesintroducing a cannulated distractor into the disc, the distractoroperable to distract the adjacent vertebrae. The distractor includes alumen in communication with the disc space through which the fluenttreatment material is injected.

Various fluent treatment materials are contemplated depending upon thecondition of the vertebral endplates and the nature of the disease ordefect of the endplates. For instance, the fluent treatment material canbe a decalcifying agent that is operable to remove calcification on theendplates. The decalcifying agent can be an acid such as EDTA.

In other cases, the endplates suffer from poor vascularity so thepre-treatment fluent material is operable to improve the vascularity ofthe endplates. Thus, in certain embodiments, the fluent treatmentmaterial is a VEGF (vascular endothelial growth factor). In otherembodiments, the material can be a gene therapy material operable totransfect cells for the expression of a pre-determined cytokine.

Other treatments of the invention operate to enhance the integration ofan implant or prosthesis with the vertebral endplates. Such fluenttreatment materials can include biomaterials capable of digesting orremoving proteoglycans that are detrimental to this integration. Such amaterial can include hyaluronidase.

Cell migration between the endplates and the prosthetic materialsubsequently introduced into the disc space can also be of concern.Certain pre-treatment materials can improve the cell migrationcharacteristics of the vertebral endplates. For instance, trypsin canaffect proteoglycan structures that reduce cell migration through theendplates.

Preferably, the step of injecting a fluent treatment includes providinga substantially enclosed volume around the portion of the endplate torestrict exposure of endplate other than said portion to said fluenttreatment. In other words, some portions of the endplate may be adequateand may not require a pre-treatment. Thus, one aspect of the inventioncontemplates a device having a central body configured to be receivedwithin the disc space. The body defines a central lumen therethrough anda number of openings in communication with the lumen, with means at theproximal end of the device for fluidly connecting to a source of thefluent treatment material to be applied to the vertebral endplatesadjacent the disc space.

The device can include at least two legs extending from the body andconfigured to contact a vertebral endplate. The legs are disposed onopposite sides of at least some of the number of openings to define anenclosed volume about the openings when the legs are in contact with avertebral endplate. The legs can be rigid to provide distractionsupport, or can be in the form of a conformal seal. With eitherapproach, the legs help contain the fluent treatment material about theaffected portion of the intervertebral endplate, and help preventcontact between the fluent material and other portions of the endplatethat may not require treatment.

It is one object of the invention to provide a method for pre-treatingan intervertebral disc to enhance the ability of a subsequentlyintroduced prosthesis, graft or implant to become integrated into thedisc space. Another object is realized by features of the invention thatprovide specific treatments for specific conditions of the vertebralendplates that have resulted from disease or defects.

Other objects and certain benefits of the invention will become apparentfrom the following written description, taken together with theaccompanying figures.

DESCRIPTION OF THE FIGURES

FIG. 1 is a lateral view of the spine illustrating the physicalcomponents of an intervertebral disc and adjacent vertebrae.

FIG. 2 is a lateral view a disc and adjacent vertebrae with a guide wireplaced in accordance with one aspect of the present invention.

FIG. 3 is a sagittal view of the disc space shown in FIG. 2 with atrephine forming a portal in the annulus fibrosus of the disc.

FIG. 4 is a sagittal view of the disc space shown in FIG. 3 with atissue extraction device positioned within the nucleus pulposus of thedisc.

FIG. 5 is a sagittal view of the disc space shown in FIGS. 2-4 with acannulated distractor in accordance with one embodiment of the presentinvention.

FIG. 6 is a lateral view of the disc space shown in FIGS. 2-5 with thetip of the cannulated distractor of FIG. 5 positioned within the discspace.

FIG. 7 is an A-P view of a disc space with a cannulated distractor,shown in cross-section, in accordance with a further embodiment of theinvention that provides for concentrated treatment of the vertebralendplates.

FIG. 8 is a perspective view of the cannulated distractor shown in FIG.7.

FIG. 9 is an end cross-sectional view of an alternative embodiment of acannulated distractor similar to the distractor shown in FIG. 7 and 8.

DESCRIPTION OF THE PREFERRED EMBODIMENTS

For the purposes of promoting an understanding of the principles of theinvention, reference will now be made to the embodiments illustrated inthe drawings and described in the following written specification. It isunderstood that no limitation to the scope of the invention is therebyintended. It is further understood that the present invention includesany alterations and modifications to the illustrated embodiments andincludes further applications of the principles of the invention aswould normally occur to one skilled in the art to which this inventionpertains.

The present invention contemplates a procedure and device that isimplemented following removal of a portion or substantially all of thenatural nucleus pulposus of an intervertebral disc. This procedure mayalso involve removal of the inner annulus fibrosus, a structure known toprimarily resist compressive loading. When disc material is removed, itis important to maintain the proper disc height during the introductionof a biomaterial that is intended to replace the removed nuclearmaterial. Removal of disc material can be accomplished chemically, suchas by the use of Chymopapain. However, the more common approach is bydiscectomy, which can be conducted as an open surgical procedure, viamicroscope-assisted visualization, or through percutaneous access.

A typical percutaneous discectomy procedure is illustrated in FIGS. 2-4.In the first step, a guide wire G is directed into an affected disc Dbetween two vertebrae, such as the L2 and L3 lumbar vertebrae. As shownin FIG. 2, the guide wire G penetrates the annulus fibrosus A and thenucleus pulposus N, and it preferably anchored at opposite sides of theannulus A. The guide wire G can be positioned and placed under indirectvision, such as fluoroscopy, or stereotactically, or using other knownprocedures for properly orienting the guide wire within the spinal discD. The procedure shown in the figures utilizes a posterior approach,which is preferable for implementation of the present invention. Ofcourse, other approaches may be utilized for the discectomy inaccordance with known surgical procedures. In addition, the accesslocation may be dictated by the location of a fissure or herniation ofthe disc.

A trephine T is advanced over the guide wire and driven through theannulus A, thereby forming a portal into the disc nucleus. As shown inFIG. 4, a tissue removal device R can be advanced through the trephine Tor through a working channel cannula aligned with the disc portal. Thedevice R can then be used to remove all or part of the nucleus N of thedisc D. As depicted in dashed lines in FIG. 4, a second trephine T′ canbe used to create a second annular portal to facilitate complete removalof the nucleus pulposus of the disc. The tissue removal device R can beof a variety of types, such as a rongeur, tissue morcellator, rotaryand/or reciprocating vacuum-assisted cutter, and even a chemicalintroducer to direct a chemical such as Chymopapain into the nuclearspace. Removal of the nucleus leaves a cavity C (see FIG. 5) surroundedby the substantially intact annulus A

The present invention contemplates the introduction of a biomaterialinto the disc cavity C that is capable or restoring disc height andpreferably substantially normal disc function. For instance, any of thebiomaterials discussed above can fill the newly formed cavity. Inaccordance with the preferred embodiment, the biomaterial is a fluidwith an appropriate flowability and/or viscosity. In particular, thebiomaterial must have sufficient flowability to permit relatively easyintroduction into the disc cavity C, but with sufficient viscosity tohold its shape within the disc. Since the material being used to fillthe disc cavity C is a fluid, the present invention provides means forholding a proper disc height as the material flows into the cavity, tothereby ensure that the cavity is filled—i.e., that the volume ofimplant biomaterial is the same as the volume of nucleus pulposusremoved in the discectomy. Moreover, the methods and devices of theinvention provide a means for maintaining the cavity volume as thebiomaterial transforms to its solid state.

Prior to the introduction of the above-mentioned biomaterial, thepresent invention contemplates a process for the pretreatment of thevertebral endplates E₁ and E₂. The goal of this process is to restorethe endplates as closely as possible to their natural state prior todisease or degeneration. The nature of the treatment will depend uponthe form of the endplate degeneration and on the type of scaffoldingthat is intended to be introduced in the nuclear cavity C.

Decalcification of the Vertebral Endplates

Calcification of the articular cartilage of the endplates impedes fluiddiffusion across the calcified zone Z, shown in FIG. 6. The endplatecontains nourishing channels in the form of vascular buds. Blood vesselsextend from the subchondral bone of the vertebral body into the surfaceof the endplate where they branch into capillaries. With increasing age,cartilaginous endplates mineralize and this calcified cartilage isgradually replaced with bone. In addition, arterioles, capillaries andvenules in the bony nutrient spaces and canals adjacent to the disc canbecome thickened or clogged with proteoglycans, and are oftenobliterated with carbohydrate containing moieties.

Thus, one treatment in accordance with the present invention is toremove calcifications on the vertebral endplates. Organic compounds areknown that are capable of binding calcium and other metals, which caninclude, but is not limited to, EDTA (ethylenediamine tetra-aceticacid), formic acid, and other dilute acids. When the organic compoundsbind to the detrimental metals, the resulting combination can be flushedfrom the disc space to eliminate the endplate calcification.

Calcification impedes fluid diffusion across the endplates. In addition,it has been found that large proteoglycans, such as aggrecan, can alsohinder the passage of certain solutes through the endplates. The removalof these proteoglycans via an appropriate enzyme, such as trypsin, canfurther enhance the permeability of the endplate. In a typicalembodiment, this treatment will accompany treatment for calcification.

Improve Vascularity of the Endplates

Vascularity through the endplate is, of course, critical to properbiological functioning of the disc. Certain health conditions canexacerbate the decrease in vascularity normally associated with aging.For instance, nicotine can cause a reduction in vascular buds and aninterruption of the vascular networks in the vicinity of the endplate.Chemical treatments are known that increase vascularity in tissues, suchas cytokines and growth factors capable of inducing endothelial cellgrowth (e.g., VEGF, vascular endothelial growth factor).

The present invention contemplates treatment of the vertebral endplatesin this manner If it is determined that the endplates suffer from poorvascularity. In the case of an elderly patient, poor vascularity can bepresumed and the treatment administered without separate verification.Alternatively, the status of the vertebral endplates can be verifiedunder direct vision, such as through an endoscope inserted into thenuclear cavity C, or indirectly, such as by way of a CT scan, MRI, PETor comparable scanning technology. This same verification process can beutilized to evaluate the extent of calcification, if any, of theendplates in anticipation of application of a decalcifying agent asdescribed above.

Enhance Integration of Prosthesis/Graft with the Endplates

Systems have been under investigation for some time for the replacementor augmentation of the disc by introducing either a partial or a totalnuclear prosthesis. Solid or injectable in situ curable biomaterialsrequire that the prosthesis stay well fixed within the disc space.Anchorage and integration at the graft-host interface (i.e., between theprosthesis and the endplates) is extremely desirable, and in some casesessential to the viability of the prosthesis. However, the cartilaginousendplates and the annulus fibrosus contain abundant large and smallproteoglycans that may impede integration between these tissue and theprosthesis.

Clinical researchers have proposed enzymatic digestion of cartilagedisruptions to denude it of proteoglycans and allow for interdigitationwith the newly synthesized matrix components. It has been found that aprotease treated matrix has much less structured water and matrix, andis more easily infiltrated with newly synthesized matrix from repairtissue. More specifically, it is known that trypsin is an enzyme thatclips the core protein of aggrecan and other matrix proteoglycans,leaving the collagenous scaffold intact. Pre-treatment of affectedendplates with trypsin will allow cartilaginous tissue buds to extendfrom adjacent tissue into a pre-treated graft to create an undulating,well-integrated surface at the graft-tissue interface.

Hyaluronan is another major component of the cartilaginous endplates,forming the backbone of the large proteoglycan aggrecan. Hyaluronidaseis used to digest aggrecan by proteolytic attack of the hyaluronanbackbone. It has been demonstrated that a sequential digestion of thecartilaginous matrix with hyaluronidase followed by trypsin effectivelyextracts proteoglycan without any significant disruption of theunderlying collagen fiber network.

Thus, in one aspect of the invention, the affected endplates can betreated with trypsin, or with the sequential application ofhyaluronidase and trypsin. Again, as with the treatments mentionedabove, the state of the endplates can be first verified before anychemicals are introduced into the nuclear cavity C. Certainly, if theendplates exhibit defects and/or calcification, all of the abovetreatments, including the treatment to enhance integration, may beindicated. On the other hand, the nature of the graft or prosthesis maymilitate in favor of pre-treating the endplates, and even the annulusfibrosus, with materials to enhance integration.

Enhance Cell Migration from the Endplate to the Scaffold

Tissue engineering involves the use of systems of cells, scaffolds andgrowth factors/cytokines to reconstruct and regenerate tissues andorgans. Certain disc prostheses may be populated with cells from thepatient's own natural disc prior to injection. Cells may also beharvested from other cartilaginous tissues of the body, such as thenon-articulating areas of hyaline cartilage in the knee. Adultmesenchymal stem cells may be isolated and purified from bone marrow oradipose tissue.

However, accessing, isolating and purifying cells in this manner canpose a host of problems. One way to avoid these problems, and one waythat is well-suited for the present invention, is by implanting anacellular scaffold. In this approach, cells are not actually placedin/on the scaffold, but are instead allowed to migrate into and populatethe scaffold. It has been found that the trypsin pre-treatment ofcartilage explants allows chondrocytes to proliferate and rapidlyreplenish matrix lost during the trypsin treatment. Removal of theextracellular matrix induces chondrocytes to resume DNA synthesis and toproliferate.

The present invention contemplates performing one or more of the abovetreatments to the intervertebral space and vertebral endplates prior tointroduction of the prosthetic scaffold, whether a solid implant or acurable fluent biomaterial. It can be noted that some treatmentsaccomplish multiple objectives. For instance, trypsin functions tocleave proteoglycans which increases endplate permeability and enhancescartilage integration with the graft/scaffold. While trypsin affectsproteoglycan structure, it does not affect or disturb the structuralintegrity the collagen-rich outer annulus fibrosus.

In one specific procedure according to the present invention, aftercompletion of the discectomy, the disc space is assessed to determineits condition, and primarily the condition of the vertebral endplates.If it is determined (or assumed) that the endplates are calcified withinthe nuclear cavity, the disc can be treated with a decalcifying agentsuch as EDTA or some other dilute acid. The decalcifying agent ismaintained in contact with the endplates over a suitable incubationduration, after which the agent, along with the byproducts of itsoperation, can be flushed from the disc space.

Next, a solution can be introduced to cleave the proteoglycans in theendplates. In a preferred embodiment, that solution is trypsin. In aspecific embodiment, the trypsin can be provided in a 0.25%-10% solutionwith its incubation time a function of the solution strength. Forexample, a 0.25% solution may require up to six hours, while a 10%solution may only need to operate for ten minutes. Other solution can beused, such as hyaluronidase (e.g., 0.2% for 2 hours, or 4% for 5-10minutes), or chondroitinase ABC. Once the incubation time has expired,the solution and its byproducts are flushed from the disc space and thecavity is well irrigated, such as with a saline solution.

If vascularity is an issue, various cytokines and/or growth factors canbe injected into the nuclear cavity. One preferred material is VEGF.Nominally, the materials in this treatment become absorbed into theendplates so only a minimal incubation time may be necessary, and noflushing would be required after application of the treatment. Besidesdirect delivery of cytokines, known methods of gene therapy may be usedto transfect resident cells (e.g., chondrocytes or endothelial cells) ona transient basis to secrete the cytokine of interest. Since this cellgrowth stimulating material is intended to remain, this treatment can bereserved to the end of the process, where other treatments requireflushing of the material after application.

If it is desired to enhance cartilage integration, the trypsin treatmentmentioned above can be utilized. Other components of the extracellularmatrix may also be targeted by appropriate materials, such asproteolytic enzymes. A proteolytic inhibitor may be necessary followingincubation to de-activate the protease or enzyme. Collagen can beremoved using a collagenase. General matrix cleavage can be accomplishedwith pronase, protease K and papain. In this step, a “cocktail” ofvarious enzymes can be injected and incubated to optimize matrix removaland subsequent integration.

In accordance with one aspect of the invention, means are provided forintroducing the various chemical treatments into the nuclear cavity C,and particularly to direct the treatments to the vertebral endplates.The invention contemplates a cannulated distractor 10 as shown in FIGS.5-6. In order to ensure that the injectable material reaches theendplates, it is important that the disc space retain its normal height.A certain amount of distraction can be accomplished by positioning ofthe patient. However, the cannulated distractor ensures that theadjacent vertebrae are properly distracted.

The distractor 10 includes a distal end 12 that extends into the disccavity C and a proximal end 14 that is configured to engage a device forinjecting the fluent material into the disc space. The distractor 10includes a cannula 11 that terminates in a distraction tip 18 at thedistal end of the device. A lumen 16 is defined along the entire lengthof the device from the proximal end 14 to the and through thedistraction tip 18. The distraction tip 18 is sized to extend throughthe portal formed in the disc annulus A (see FIG. 3). The distractor 10can include a shoulder 20 proximal to the distraction tip 18, in whichthe shoulder is sized to prevent passage through the annular portal. Theshoulder 20 can operate to limit the distance that the distraction tip18 extends into the disc cavity C.

As shown in FIG. 6, the distraction tip 18 is intended to be insertedthrough the annular portal and is configured to restore the appropriateintradiscal height in the cavity C. Thus, in one embodiment, thedistraction tip 18 can include a tapered leading portion 19. Thisleading portion 19 can be introduced into the cavity C and as the tip isadvanced further into the cavity the leading portion will graduallydistract the adjacent vertebrae as the leading portion 19 bears againstthe disc endplates E₁ and E₂. In a specific embodiment, the taperedportion 19 can be substantially bullet-shaped, as shown in FIG. 6. Withthis configuration, the distraction tip 18 can have any rotationalorientation when the tip is inserted through the annular portal. Otherforms of distraction tip 18 are contemplated as appropriate for theparticular patient anatomy, as well as appropriate for the configurationof the portal formed in the annulus fibrosus.

Referring to FIG. 6, in accordance with one feature of the invention,the distraction tip 18 includes a number of side orifices 22 and an endorifice 24 that all communicate with the central lumen 16. The orifices22, 24 provide an exit path for fluid injected through the lumen 16. Theorifices are oriented to be unobstructed by the vertebral endplates E₁and E₂, and most preferably are oriented to direct the fluent materialdirectly onto the endplates.

Since fluid is intended for introduction through the distraction tip 30,it is preferable that some feature be provided to ensure a substantiallyfluid-tight seal at the entrance to the disc cavity C through theannular portal. Thus, in one embodiment of the invention, thedistraction tip 18 can include annular rings 26 that are intended tobear against the disc endplates E and/or the disc annulus A in a sealingrelationship. The rings 26 can be integral with the distraction tip 18,or can be separate components mounted on the distraction tip, such as inthe form of elastomeric seal rings.

The distractor 10 includes a fitting 28 defined at the proximal end 14of the cannula 11. The fitting 28 provides means for making afluid-tight connection with a device adapted to inject the fluentmaterial into the disc. In a specific embodiment, the fitting 28 is auniversal fitting, such as a LUER® fitting. This fitting can engage asyringe or another other suitable injector device. In addition, in orderto flush the disc cavity C following a particular treatment, the fittingcan be adapted to engage a lavage and a suction device. The lavage caninclude pulsatile filling of the cavity with a neutral fluid, such assaline, and then removal of the fluids by an appropriate suction device.Optimally, the suction device can simply constitute a syringe that canbe manually operated to withdraw the minimal amount of fluid within thecavity without risk of generating unhealthy suction pressure.

As explained above, the cannulated distractor 10 of the presentinvention is utilized after a discectomy procedure. For purposes ofillustration, it has been assumed that a total discectomy has beenperformed in which substantially all of the nucleus pulposus has beenremoved, leaving a disc cavity C as shown in FIG. 5. If a bilateralapproach has been used (as represented by the first and second trephinesT and T′), one of the annular portals can be sealed with a materialcompatible to the disc annulus fibrosus. When the nucleus has beencleared, the guide wire G can be repositioned within the disc D, againpreferably using known guidance and positioning instruments andtechniques. The cannulated distractor 10 can then be advanced over theguide wire until the distraction tip 18 is properly situated within thenuclear cavity C. Preferably, the proper depth for the distraction tip18 can be determined by contact of the shoulder 20 with the outerannulus A.

The tapered portion 19 of the distraction tip gradually separates theadjacent vertebral endplates E₁ and E₂ as the distraction tip 18 isdriven further into the disc space. A mallet, impactor or other suitabledriver can be used to push the tapered portion 19 into position againstthe natural tension of the disc annulus. It is understood that the goalof this step is to fully distract the intervertebral space to a properdisc height for the particular spinal level. For instance, for the L2-L3disc space, the appropriate disc height may be 13-15 mm, so that thedistraction tip is positioned within the cavity C to achieve this amountof distraction. As shown in FIG. 5, preferably only one cannulateddistractor 10 is utilized, since the distraction tip 18 necessarilyoccupies a certain portion of the volume of the cavity C. However, asecond cannulated distractor and associated distraction tip may benecessary (such as through a second annular portal as shown in FIG. 4)to achieve the proper disc height.

When the distraction tip, such as tip 10, is inserted to its properdepth within the disc cavity C, the annular portal is sealed, whether bycontact with the shoulder 20, or by engagement of the rings 26 with theendplates E₁ and E₂ or the interior of the annular portal. At thispoint, the fluent treatment material can be injected into the cannulateddistractor, and specifically through the lumen 16, once the guide wire Ghas been removed. The treatment material exits through the orifices 22,24 in the distraction tip 18 to fill the cavity C. The orifices 30, 32are preferably positioned and sized to achieve complete and rapiddispersion of the material throughout the cavity.

It should be apparent that the distraction tip 18 maintains the properdisc height while the treatment material is injected. The tip can beretained in position until the injected material has had time toincubate or perform its essential function. Where the incubation time isshort, the entire treatment process can occur in a single surgicalprocedure. However, where the incubation time is lengthy (such as thesix hour trypsin incubation time mentioned above), it may be desirableto temporarily close the surgical wound. Since the present inventioncontemplates introduction of the fluent treatment material through acannulated distractor, minimally invasive techniques can be utilized,which means the surgical wound is minimal.

In certain embodiments, the cannulated distractor, such as thedistractor 10 shown in FIG. 5, can be left in position. The proximal end14 can be sealed while the treatment material incubates. Alternatively,the distraction tip 18 can be removable from the cannula 11 so that thecannula can be removed while the tip is kept in its distractionposition. Thus, the tip 18 and cannula 11 can be provided with aremovable mating element 19, such as a press-fit (as shown in FIG. 8) ora threaded or LUER® type fitting (not shown) as would occur to a personof skill in this art. Once the pre-treatment material has incubated, thedistraction tip 18 can be removed, whether the tip is separate or isintegral with the cannula 11.

As described above, the cannulated distractor 10 is initially used forthe pre-treatment of the disc space in accordance with the presentinvention. Once the pretreatment has been completed, the cannulateddistractor can then be used for the injection of a curable biomaterialof the type described above. Use of the cannulated distractor for thispurpose is disclosed in provisional application Ser. No. 60/336,002,entitled “Devices, Methods and Assemblies for Intervertebral Disc Repairand Regeneration”, filed on Nov. 1, 2001, and co-pending utility patentapplication Ser. No. ______, entitled Devices and Methods for theRestoration of a Spinal Disc, and filed on Oct. ______, 2002 whichclaims priority to the first mentioned provisional application. Thedisclosures of both applications are incorporated herein by reference.

The distractor 10 in the prior illustrated embodiment provides a fluidpassageway for dispersing the fluid throughout the entire disc cavity C.In some cases, only a portion of the intervertebral endplate is diseasedor damaged and in need of some form of pre-treatment. In that case, itis not desirable to expose healthy endplate or even healthy innerannulus fibrosus to the pre-treatment materials. In an alternativeembodiment, shown in FIG. 7, a cruciate distraction tip 30 is depicted.The tip 30 includes a central lumen 32 defined in a central body 34. Anumber of openings 36 extend from the central lumen 32 to provide apassageway for the pre-treatment fluid material.

The cruciate distraction tip 30 includes a number of legs 38 projectingoutward from the body 34 and into contact with the vertebral endplatesat opposite sides of the disc cavity C. As with the distraction member10 of the prior embodiment, the cruciate tip 30 is configured todistract the adjacent vertebrae and to hold a proper disc height as thetreatment fluid is introduced into the disc space and incubated.However, unlike the prior embodiment, the tip 30 of FIGS. 7, 8 providesmeans for focused treatment of the endplates. Thus, the legs 38 serve tocreate an essentially sealed area between the legs and the central body34. In this way, fluid dispersed from the openings 36 will be exposed toonly a specific portion of the vertebral endplates. This approach isespecially useful when it is determined that only discrete portions ofthe endplates are diseased or damaged to a point that requirespre-treatment. The legs 38 then operate as a dam to contain thetreatment fluid and prevent the fluid from contacting portions of theendplates that are otherwise acceptable.

In the illustrated embodiment of FIG. 7, the openings 36 provide a fluidpath to discrete portions of the opposite endplates. Alternatively, theopenings can be concentrated to one side so that the fluid treatment isapplied to a portion of only one endplate.

As shown in FIG. 8, the distraction tip 30 can extend from a cannula 40that can be similar to the cannula 11 described above. The tip can beintegrally formed with the cannula, but is preferably detachable. Asalso shown in FIG. 8, the central lumen 32 terminates in an opening atthe end of the tip, since the purpose is to limit the exposure of thepre-treatment material. With the embodiment shown in FIG. 8, it iscontemplated that the distraction tip 30 will span the disc space sothat the distal end of the tip will bear against the disc annulusopposite the annular portal through which the cannula 40 extends. Inthis way, the annulus can help seal the end of the channel formedbetween the legs 38 of the cruciate distraction tip. Alternatively, thedistraction tip can be formed with a web at the distal end of the tip,in which the web is co-extensive with the legs to form a fully enclosedvolume.

The same concept of limited pre-treatment of the vertebral endplates canbe accomplished by an alternative embodiment shown in FIG. 9. In thisembodiment, a dispensing tip 50 includes a central body 51 that isgenerally tubular. The body is preferably oval in shape, as shown inFIG. 9. The body defines a central lumen 52 that communicates with anumber of openings 54. In this embodiment, the dispensing tip 50includes legs 56 that extend from the body that are in the form of aconformal seal. In this embodiment, the legs 56 do not serve to supportthe adjacent vertebrae, but are instead operable only to create a sealedvolume about a specific region of the vertebral endplates. The legs cantherefore be formed of a resilient material, such as a biocompatiblepolymer, that may be different from the material of the central body 51.

The dispensing tip 50 can be connected to a cannula, as with theprevious embodiments, either integrally or by some form of removableattachment. Since the tip 50 is not intended to provide a distractioncapability, it can be maintained in position by the cannula.

In accordance with certain embodiments, the cannulated distractors, andparticularly the distraction tips, described above can be formed avariety of bio-compatible materials. As explained above the distractiontips must be sufficient strong to maintain proper distraction of thedisc space until the biomaterial has been fully injected and cured, ifnecessary. In certain embodiments, the distraction tips are formed of abio-compatible metal, such as stainless steel or titanium. In otherembodiments, the distraction tips are formed of a polymer or plasticthat is preferably radiolucent to permit visualization of thedistraction tip in situ to verify the position of the component. Inother embodiments, the distraction tip can be formed of a bio-resorbablematerial.

While the invention has been illustrated and described in detail in thedrawings and foregoing description, the same should be considered asillustrative and not restrictive in character. It is understood thatonly the preferred embodiments have been presented and that all changes,modifications and further applications that come within the spirit ofthe invention are desired to be protected.

1-21. (canceled)
 21. A method of providing nutrients to anintervertebral disc situated between the endplates of upper and lowervertebrae, comprising the steps of: forming a passageway into the discspace; placing a cannulated element in the passageway; and providing oneor more substances beneficial to the intervertebral disc through thecannulated element.
 22. The method of claim 21, wherein the beneficialsubstances include a therapeutic agent.
 23. The method of claim 22,wherein the therapeutic agent includes a growth factor.
 24. The methodof claim 21, further including the step of transplanting cells ortissues into the disc.
 25. The method of claim 21, further including thestep of providing a reservoir containing the beneficial substance incommunication with the cannulated element.
 26. The method of claim 21,further comprising the step of removing at least a portion of thenucleus pulposus of the intervertebral disc to expose at least a portionof the endplate of an adjacent vertebra to the disc.
 27. The method ofclaim 26, wherein the beneficial substance includes a fluent materialoperable to prepare the portion of the endplate to accommodate a discprosthesis or graft subsequently introduced into the disc space.
 28. Themethod of claim 27, wherein the fluent material is a vascular growthfactor.
 29. The method of claim 27, further comprising the step ofretaining the fluent material within the disc space for an incubationperiod sufficient for substantially complete operation of the fluentmaterial on the portion of the endplate.
 30. The method of claim 21,further comprising the subsequent step of flushing the disc space toremove at least portion of the beneficial substances and any byproductsthereof.
 31. The method of claim 21, further comprising the step ofmaintaining the upper and lower vertebrae in a distracted position whilethe beneficial substance is provided through the cannulated element. 32.The method of claim 31, wherein the cannulated element is a cannulateddistractor operable to distract the upper and lower vertebrae andincluding a lumen in communication with the disc space through which thefluent treatment material is injected.
 33. A method of improvingnutrient flow into the intervertebral disc space situated between theendplates of upper and lower vertebrae, comprising the steps of:extending a cannulated element into the disc space between theendplates; and introducing through the cannulated element one or moresubstances beneficial to improving nutrient flow into the disc space.34. The method of claim 33, wherein the beneficial substances contain atherapeutic agent.
 35. The method of claim 34, wherein the therapeuticagent includes a growth factor.
 36. The method of claim 33, furtherincluding the step of transplanting cells or tissues into the disc. 37.The method of claim 33, further including the step of providing areservoir containing the beneficial substance in communication with thecannulated element.